Trans-fused rings

Stork-Eschenmoser Hypothesis- Olefin Geometry is preserved in the cyclization reaction, i.e. trans olefin leads to a trans fused ring jucntion A. Eschenmoser HCA 1955, 38, 1890 G. Stork JAGS 1955, 77, 5068... 

In the synthesis of ( )-palominol and ( )-dolabellatrienone from famesol, Corey and Kania84 employed a dianion accelerated oxy-Cope rearrangement to form the 11,5-trans-fused ring system of the dolabellanes. Diol 112 was treated with potassium hydride in THF to afford a 1 1 mixture of products with iraws-ll,5-fused ring systems, 113 and... 

The intramolecular acid-catalyzed reacdon of 2-propargylsilanes of structural type (117) with N-acy-liumion ion precursors leads to bridged azabicyclic ring systems (118 Scheme 33) which contain an a-allenic amide fimcdon. These bicyclic products serve as intermediates to highly funcdonalized trans-fused ring systems possessing a 1,3-diene moiety. 

Due to a deformation of the cyclohexane ring, c/5 -hydrindane (the numbers in [ ] refer to carbon atoms between the bridgehead carbons) is only slightly less stable than the trans isomer ( 1 kcal/mol). 8-Methylhydrindane is of interest since it occurs as part structure of the C/D rings of steroids (as a trans fused ring system). Introduction of an angular CH3 group makes the cis isomer more stable than the trans because the cis isomer has fewer 1,3-diaxial interactions. 

In summary, the stereochemical course of cation-7t cyclizations is determined by stereoelectronic and conformational effects. Concerted cation-Ti cyclizations usually involve a stereospecific trans-addition (axial attack) of the carbocation to the double bond. This is exemplified by Johnson s biomimetic synthesis ( )-progesterone, which possesses a trans, anti, trans-fused ring system." - ... 

The polymers with trans-fused five-membered rings linked with a diisotactic head-to-tail sequence have chirality, although the polymers composed of the cis-fused ring are achiral. Scheme 10 summarizes the structures of the stereoisomeric polymers. The optically active zirconocene complex with a C2 symmetric structure catalyzes the enantioselective cyclopolymerization of 1,5-hexadiene (Eq. 20) [98, 99]. Although the polymer contains not only trans-fused ring but also cis-fused ring units (ca. 68 32), it shows optical rotation due to the main chain chirality. 

The structural diversity and pharmacological activity associated with this class of alkaloids have stimulated synthetic activity by numerous groups[23]. However, the route which can be applicable to the synthesis of both cis- and trans-fused ring systems has been reported only to a limited extent[24]. Moreover, no methodology for the divergent synthesis of the 2,Sa-cis and -trans substituted ring system has been reported to date. 

Of special interest for practical applications, as well as for future receptor studies, are the structure-activity relationships of the brassinosteroids. As postulated (6) the structural requirements for a high activity are the following (22R.23R)-vicinal diol moiety (24S)-methyl- or ethyl group 7-oxa-lactone or 6-oxo functionality 3a-hydroxy group, 2a,3a-vicinai diol or 3a,4a-vicinal diol and A/B-trans-fused ring junction. 

We have seen that rings can be trans fused or cis fused and that trans fused rings are more stable (Section 2.15). In steroids, the B, C, and D rings are all trans fused. In most naturally occurring steroids, the A and B rings are also trans fused. 

Proton-catalyzed olefin cyclizations of open-chain educts may give tri- or tetracyclic products but low yields are typical (E.E. van Tamelen, 1968,1977 see p. 91). More useful are cyclizations of monocyclic educts with appropriate side-chains. The chiral centre to which the chain is attached may direct the steric course of the cyclization, and several asymmetric centres may be formed stereoselectively since the cyclizations usually lead to trans-fused rings. 

Just as cyclohexane can be drawn in a chair conformation, the three-dimensional representation for 5a-cholestane is shown by the following conformational formula. Although cyclohexane may undergo a flip in conformation, steroids are rigid structures, because they generally have at least one trans fused ring system and these rings must be diequatorial to each other. 

Brevetoxin B has 23 chiral centers as well as 11 trans-fused rings. While it has far fewer chiral centers than palytoxin (page 331), the... 

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